Portopulmonary HypertensionPhase 3PortopulmNCT01224210
Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial
A Phase 3 study testing Ambrisentan in people with Portopulmonary Hypertension, run by Tufts Medical Center at 6 sites in United States.
Trial summary
This is an Open Label, Multicenter, pilot clinical trial to assess the efficacy and safety of an oral selective Endothelin Receptor Antagonist (ambrisentan) in patients with portopulmonary hypertension. Preliminary evidence suggests that ambrisentan is safe and effective in patients with portopulmonary hypertension. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Portopulmonary Hypertension
- What is being tested?
- Ambrisentan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 6 sitesUnited States
- Study dates
- Mar 2010to Mar 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects need to fulfill all of the following 4 criteria:
- Evidence of portal hypertension (by hemodynamic measurement, or by Doppler flow of portal circulation, or by clinical evidence of portal hypertension such as esophageal or gastric varices, as evidenced by prior upper endoscopy).
- Evidence of pulmonary arterial hypertension by right heart catheterization (all three criteria need to be present) Right heart catheterization may have been performed up to 30 days prior to screening
- Mean PAP (pulmonary artery pressure) >25 mm Hg, and
- PVR (pulmonary vascular resistance) >240 dynes/s/cm5, and
- TPG (transpulmonary gradient = meanPAP -PAWP) >12 mm Hg
- Baseline AST, ALT < 5 times the upper limit of normal, total Bili < 3.0 mg/dl, and mild liver impairment with Child -Pugh class A or B
- Ages 18 years and above
Who cannot join
- Presence of any other etiology of pulmonary arterial hypertension (HIV, connective tissue disease, sickle cell, left heart failure, chronic thromboembolic PH, etc)
- Treatment with prostacyclins, other ERAs, or PDE5 inhibitors within 30 days of enrollment.
- Moribund state or anticipated death within 1 month.
- AST or ALT ≥ 5 times upper limit of normal
- Total bilirubin ≥ 3.0 mg/dl
- Significant lung disease (obstructive lung disease with FEV1 < 1L, or FEV1/FVC <50%; or restrictive lung disease with Total Lung Capacity < 60% predicted). PFTs may have been performed up to 6 months prior to enrollment.
Show all 9Show fewer
- Pregnancy
- Age <18 years
- Child -Pugh class C
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Tufts Medical Center
Boston, Massachusetts, 02111
University of North Carolina
Chapel Hill, North Carolina, 27599
The Ohio State University Medical Center
Columbus, Ohio, 43221
UT Southwestern Medical Center
Dallas, Texas, 75390
Mayo Clinic Florida
Jacksonville, Florida, 32224
UCSD Medical Center
La Jolla, California, 92093
About this study
This is an Open Label, Multicenter, pilot clinical trial to assess the efficacy and safety of an oral selective Endothelin Receptor Antagonist (ambrisentan) in patients with portopulmonary hypertension.
Preliminary evidence suggests that ambrisentan is safe and effective in patients with portopulmonary hypertension. The goal of therapy for these patients is to improve symptoms of dyspnea and to improve pulmonary hemodynamics to a mean pulmonary artery pressure <35 mm Hg in order to make patients eligible for liver transplantation. Therefore, the primary endpoints for this study will include 6 minute walk distance (6MWD) and pulmonary vascular resistance (PVR).
Eligible subjects will receive 5 mg ambrisentan once-daily for the first 4 weeks. After the initial 4-week period, investigators will increase study drug dose to 10 mg once daily (both 5 mg and 10 mg doses are FDA approved). If 10 mg is not tolerated in the opinion of investigator, then the investigator may decrease the dose back to 5 mg once daily. Primary outcome is a change in both the 6 Minute Walk Distance and in Pulmonary Vascular Resistance from baseline to Week 24. Subjects will be monitored with liver function tests (LFT) every 2 weeks for the first 8 weeks, then every 4 weeks thereafter. These safety laboratory tests may be performed at a local phlebotomy laboratory or at the Investigator clinic. In addition, the Investigator will assess each subject for safety and efficacy at Week 4, Week 12, and Week 24. Following Week 24, subjects will be assessed for safety and efficacy every 12 weeks. Patients will be followed for a total of 1 year. After 1 year, if the Investigator feels that continuing the treatment will be beneficial to the patients, they will be provided with ambrisentan by Gilead Pharmaceuticals, free of charge.
- Conditions
- Portopulmonary Hypertension
- Being tested
- Ambrisentan
- Keywords
- portopulmonary hypertension, portal hypertension, esophageal or gastric varices, right heart catheterization, transpulmonary gradient, Endothelin Receptor Antagonist, Ambrisentan, Letairis, pulmonary hemodynamics
- Medical subject headings
- Hypertension, Portal, Esophageal and Gastric Varices
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmbrisentanDrug
Also called Letairis
Ambrisentan once-daily in the morning with or without food. The adult dose selected for this study will be 5 mg for the first 4 weeks. After the initial 4 weeks the dose will be increased to 10mg (available doses are 5, and 10 mg) based on tolerance safety. Subjects will remain on 10mg until they complete the study. Dose adjustments may be made based on side effects.
| Study group | Role | What they receive |
|---|---|---|
| Ambrisentan (24 Weeks), Extension (4 Weeks) | Other | Open Label Ambrisentan Receives: Drug: Ambrisentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pulmonary Vascular Resistance
Change in Pulmonary Vascular Resistance from baseline to Week 24 for all patients (using cardiac output [CO] measured by the thermodilution method and reported as percent difference from baseline).
Measured: from baseline to Week 24
6 Minute Walk Distance
Change from baseline in 6 Minute Walk Distance to Week 24 for all patients. (difference measured in meters).
Measured: Change from baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2010 (estimated)
- Study startMar 2010
- Primary completionOct 2016
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Portopulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Ioana Preston, MD, Principal investigator, Tufts Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01224210
- Sponsor's protocol ID
- Ambrisentan Portopulm Study
- Acronym
- Portopulm
- Status last verified
- Dec 2020
- First submitted
- 18 Oct 2010
- Last updated
- 12 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Preston IR, Burger CD, Bartolome S, Safdar Z, Krowka M, Sood N, Ford HJ, Battarjee WF, Chakinala MM, Gomberg-Maitland M, Hill NS. Ambrisentan in portopulmonary hypertension: A multicenter, open-label trial. J Heart Lung Transplant. 2020 May;39(5):464-472. doi: 10.1016/j.healun.2019.12.008. Epub 2020 Jan 21.
PubMed 32008947
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial
- ClinicalTrials.gov ID
- NCT01224210
- Acronym / sponsor ID
- Portopulm / Ambrisentan Portopulm Study
- Conditions
- Portopulmonary Hypertension
- Keywords
- portopulmonary hypertension, portal hypertension, esophageal or gastric varices, right heart catheterization, transpulmonary gradient, Endothelin Receptor Antagonist, Ambrisentan, Letairis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Tufts Medical CenterUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Mar 2010 (actual)
- Primary completion
- Oct 2016 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 19 Oct 2010 (estimated)
- Results
- Posted 12 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an Open Label, Multicenter, pilot clinical trial to assess the efficacy and safety of an oral selective Endothelin Receptor Antagonist (ambrisentan) in patients with portopulmonary hypertension.
Preliminary evidence suggests that ambrisentan is safe and effective in patients with portopulmonary hypertension. The goal of therapy for these patients is to improve symptoms of dyspnea and to improve pulmonary hemodynamics to a mean pulmonary artery pressure <35 mm Hg in order to make patients eligible for liver transplantation. Therefore, the primary endpoints for this study will include 6 minute walk distance (6MWD) and pulmonary vascular resistance (PVR).
Eligible subjects will receive 5 mg ambrisentan once-daily for the first 4 weeks. After the initial 4-week period, investigators will increase study drug dose to 10 mg once daily (both 5 mg and 10 mg doses are FDA approved). If 10 mg is not tolerated in the opinion of investigator, then the investigator may decrease the dose back to 5 mg once daily. Primary outcome is a change in both the 6 Minute Walk Distance and in Pulmonary Vascular Resistance from baseline to Week 24. Subjects will be monitored with liver function tests (LFT) every 2 weeks for the first 8 weeks, then every 4 weeks thereafter. These safety laboratory tests may be performed at a local phlebotomy laboratory or at the Investigator clinic. In addition, the Investigator will assess each subject for safety and efficacy at Week 4, Week 12, and Week 24. Following Week 24, subjects will be assessed for safety and efficacy every 12 weeks. Patients will be followed for a total of 1 year. After 1 year, if the Investigator feels that continuing the treatment will be beneficial to the patients, they will be provided with ambrisentan by Gilead Pharmaceuticals, free of charge.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ambrisentan (24 Weeks), Extension (4 Weeks) | Other | Drug: AmbrisentanOpen Label Ambrisentan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Evidence of portal hypertension (by hemodynamic measurement, or by Doppler flow of portal circulation, or by clinical evidence of portal hypertension such as esophageal or gastric varices, as evidenced by prior upper endoscopy).
- Evidence of pulmonary arterial hypertension by right heart catheterization (all three criteria need to be present) Right heart catheterization may have been performed up to 30 days prior to screening
- Baseline AST, ALT < 5 times the upper limit of normal, total Bili < 3.0 mg/dl, and mild liver impairment with Child -Pugh class A or B
- Ages 18 years and above
Key exclusion criteria (9 listed)
- Presence of any other etiology of pulmonary arterial hypertension (HIV, connective tissue disease, sickle cell, left heart failure, chronic thromboembolic PH, etc)
- Treatment with prostacyclins, other ERAs, or PDE5 inhibitors within 30 days of enrollment.
- Moribund state or anticipated death within 1 month.
- AST or ALT ≥ 5 times upper limit of normal
- Total bilirubin ≥ 3.0 mg/dl
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmbrisentanAlso: LetairisAmbrisentan once-daily in the morning with or without food. The adult dose selected for this study will be 5 mg for the first 4 weeks. After the initial 4 weeks the dose will be increased to 10mg (available doses are 5, and 10 mg) based on tolerance safety. Subjects will remain on 10mg until they complete the study. Dose adjustments may be made based on side effects. | Drug | Ambrisentan (24 Weeks), Extension (4 Weeks) |
Primary outcome
Change in Pulmonary Vascular Resistance
Time frame: from baseline to Week 24
Change in Pulmonary Vascular Resistance from baseline to Week 24 for all patients (using cardiac output [CO] measured by the thermodilution method and reported as percent difference from baseline).
6 Minute Walk Distance
Time frame: Change from baseline to Week 24
Change from baseline in 6 Minute Walk Distance to Week 24 for all patients. (difference measured in meters).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32008947Preston IR, Burger CD, Bartolome S, Safdar Z, Krowka M, Sood N, Ford HJ, Battarjee WF, Chakinala MM, Gomberg-Maitland M, Hill NS. Ambrisentan in portopulmonary hypertension: A multicenter, open-label trial. J Heart Lung Transplant. 2020 May;39(5):464-472. doi: 10.1016/j.healun.2019.12.008. Epub 2020 Jan 21.
- Individual participant dataSharing planned: No
Related trials for Portopulmonary Hypertension
Not yet recruitingObservational study
Heart Problems in Children With Chronic Liver Disease
Chronic Liver Disease (CLD), Liver Cirrhosis
Not yet recruitingObservational study
Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension
Portopulmonary Hypertension, Pulmonary Arterial Hypertension (PAH)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ioana Preston, MD principal investigator
Tufts Medical Center
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ambrisentan in people with Portopulmonary Hypertension, run by Tufts Medical Center at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pulmonary Vascular Resistance (time frame: from baseline to Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01224210, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2021.